title: Improved spatial learning in aged rats by genetic activation of protein kinase C in small groups of hippocampal neurons.
abstract: Age-related decline in human cognition is well known, and there are correlative changes in the function of neocortical and hippocampal neurons. Similarly, age-related decline in learning has been observed in rodents, including deficits in a hippocampal-dependent learning paradigm, the Morris water maze. Furthermore, there are correlative deficits in specific signaling pathways, including protein kinase C (PKC) pathways, in cerebellar, hippocampal, or neocortical neurons. PKC pathways are strong candidates for mediating the molecular changes that underlie spatial learning, as they play critical roles in neurotransmitter release and synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), and deletion of specific PKC genes results in deficits in learning. Conversely, genetic activation of PKC pathways in small groups of hippocampal or cortical neurons enhances learning in specific paradigms. In this study, the authors delivered a constitutively active PKC into small groups of hippocampal dentate granule neurons in aged rats (using a herpes simplex virus-1 vector). Aged 2-year-old rats that received the constitutively active PKC displayed improved performance in the Morris water maze relative to controls in three different measures. These results indicate that PKC pathways play an important role in mediating spatial learning in aged rats. Additionally, these results represent a system for studying the neural mechanisms underlying aging-related learning deficits, and potentially developing gene therapies for cognitive and age-related deficits.
authors.affiliation: Department of Neurology, West Roxbury VA Hospital/Harvard Medical School, West Roxbury, MA 02132, USA.
authors.forename: Guo-Rong
authors.initials: GR
authors.lastname: Zhang
authors.forename: Meng
authors.initials: M
authors.lastname: Liu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Cao
authors.forename: Lingxin
authors.initials: L
authors.lastname: Kong
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wang
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: O'Brien
authors.forename: Shuo-Chieh
authors.initials: SC
authors.lastname: Wu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Cook
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Geller
mesh_terms: D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D018259:Herpesvirus 1, Human; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D007859:Learning Disabilities / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D055647:Rats, Transgenic; D013028:Space Perception / Q000502:physiology*; D013037:Spatial Behavior / Q000502:physiology
chemical_list: D011493:Protein Kinase C